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According to the National Foundation for Cancer Research, 240,000 people worldwide are diagnosed with GBM annually.
🧠Did you know that according to the National Foundation for Cancer Research, 240,000 people worldwide are diagnosed with #GBM annually- that's equivalent to the population of Winston-Salem, North Carolina!
— Glioblastoma Research Organization (@glioblastomaorg) October 4, 2022
Source: National Foundation for Cancer Research#Glioblastoma pic.twitter.com/tY8lXrvdd4
On July 6, NWBO publicly confirmed the phase iii study was completed. Clinicaltrials.gov differentiates primary completion date from study completion date. The latter typically falls later because it encompasses not only the primary endpoint data, but the endpoint data still accumulated thereafter.
ClinicalTrials.gov Completion Dates: What They Are, & What They Are Not
The Primary Completion Date and Study Completion Date are NOT connected to:
Data analysis
Publication
Enrollment completion
IRB closure
The Study Completion Date is the date of the last study visit where data was collected for any of the study outcomes.
The Primary Completion Date is the date of the last study visit where data was collected for the primary study outcome(s). This will be the same as the Study Completion Date unless the last study visit for primary outcome data collection occurs before the last study visit where data is collected for secondary or other outcomes.
Once unblinded, researchers could see where that data was headed. My guess is the hazard ratios were headed to a very happy follow up place, so while manufacturing was still getting its act together they let the secondary data accumulate, probably with full JA and regulator support.
NWBO finally announcing trial “completed”
This Phase III trial has been completed and the top line data was presented by a key investigator at a recent scientific meeting.
This Phase III trial reached data lock and top line data was recently presented.
It’s pretty simple. Around 13% survival at five years from randomization for the original treatment group, around 10% survival at three years for crossovers from recurrence. This at least suggests, that over time, the square footage under the hazard ratio expands for the original treatment arm, and since non-crossovers are likely to do worse on average over long spans, this difference probably becomes amplified. That’s potentially good news for DCVax-l.
Hopefully, regarding placebo versus treatment, at minimum we have a trend, despite the confoundment, and that will be suggestive of further confirmation, whilst the valuation only considers the unconfounded results demonstrated via the ECA arm.
Excellent post TDD.
So ... there it was. An article from FDA by 13 FDA employees including Pazdur, that greenlit the use of ECA.
Webinar #3: Building an External Control Arm in recurrent glioblastoma
Help Joel Live Longer
On May 5, 2021 Joel had his fourth and final dose of Dendritic Cell Vaccine, (DCVax), at Kings College Hospital in London, with Professor Keyoumars Ashkan.
Update September 18, 2022.
It’s been a while since we last updated everyone. The time just seems to disappear. But we’re hugely relieved that the scan that Joel has just had in September is showing as stable, as was his last one in May. Given that he was only given 12 to 18 months to live, this scan seemed like a significant milestone, as it’s the three-year anniversary of his surgery and diagnosis. So, pretty incredible, really. It was quite poignant for Joel to get his third-year university modules on the same day as his scan results.........
Finally, we just want to thank those lovely individuals who have continued to quietly put regular donations into the crowdfund account. It never goes unnoticed and we are forever grateful.
Ian & Steph.
I agree. Thanks Dr Bala.
Thanks Basin Street Blues.
‘"paper has been submitted, keeping up fingers for the reviewers and hopefully this will be published before long."‘
Thanks Richard!
Professor Keyoumars Ashkan delivering a presentation at The First King’s Advanced Therapies Symposium on Friday 09th Sept 2022 at 11.45am.
Thanks Basin Street Blues.
Hard to decipher everything clearly.
IMO,
Min 4.07
Paper has been submitted. Single(?).......... and hopefully this is accomplished before that.
NOTBOB17,
Fetal Medicine Research Institute
16-20 Windsor Walk, London SE5 8BB
https://mobile.twitter.com/HenryMuney/status/1567174638215790593/photo/1
Thanks for sharing LearningEveryTrade.
That data has not been published and you cannot extract it from the NYAS data.
From the NYAS data nobody entered the rGBM arm after 31 months. So to live 5 years, they had to live at least 29 months past crossover And the 29 mOS post crossover was 10%. That is 6 patients at most (an very likely less as many of those 29 month post cross may well have not reached 5 months.).
mxp1,
Real-Time Oncology Review.
https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review
DL7,
thank you for sharing the story of your mother.
I'm happy she did very well from her diagnosis at the end of 2011 until about 2017.
Your mom was probably one of the early patients (n=38)enrolled between July 2007 and May 2012 with an unknown MGMT gene promoter.
Data 2017:
The MGMT gene promoter was methylated in 39.6% of patients (n?=?131) and unmethylated in 48.9% (n?=?162), with information not available for 11.5% (n?=?38; the missing data relates to the early patients enrolled a decade ago).
Missing MGMT gene promoter data = 11 DCVax-L patients.
1 “Unknown” DCVax-L patient alive 36 months from randomization.
DL7,
I'm sending you my condolences and love. Thanks for sharing her story. I'm happy for the extra 9 years you had together. Can you share if your mom was MGMT-methylated or MGMT-unmethylated GBM patient?
Written by knowledgeable people but why not check ClinicalTrials.gov?
Next Steps for Immunotherapy in Glioblastoma.
.
by Toni Q. Cao, Derek A. Wainwright, Catalina Lee-Chang, Jason Miska, Adam M. Sonabend, Amy B. Heimberger and Rimas V. Lukas
Received: 17 July 2022 / Revised: 12 August 2022 / Accepted: 17 August 2022 / Published: 20 August 2022
DCs are key players in immunosurveillance and immune regulation that present phagocytosed antigens to naïve T cells. DCVax-L is the most well-studied DC vaccine and is comprised of autologous DCs pulsed with autologous tumor lysate. The phase 3 DCVax trial (NCT00045968) investigated the impact of DCVax-L in addition to SOC (surgical resection and chemoradiotherapy) for newly diagnosed GBM patients. Due to the cross-over study design, nearly 90% of the patients in this study received DCVax-L, making an interpretation of the survival outcome challenging. In the overall intent to treat the patient population (investigational arm + control arm), the mOS was estimated to be 23.1 months. This study has benchmarked these findings to historical controls but has not yet evaluated its primary endpoint of PFS
Of note, several of these clinical trials utilized historical controls as the active comparator. Many have deemed the use of historical controls as suboptimal due to potential differences in patient, disease, and therapeutic characteristics that subsequently confound results. Furthermore, historical controls face different survival trends when matched to contemporary patients, likely as a result of evolving therapeutic options [67,68,69]. Moving forward, the reliability of historical controls should continue to be kept in mind when designing clinical trials.
Meirluc,
Rereading my old notes, I must admit that my prediction of the number of non-crossover placebo patients alive at 36 months from surgery is wrong.
Let me explain.
There are 3 placebo patients on the PFS KM curve with confirmed disease progression between 30 and 31 months from randomization = between 33 and 34 months from surgery.
I think radiographic evidence of disease progression by independent radiology review was confirmed between 35 and 36 months from surgery. So, the 3 patients were still alive at 36 months from surgery.
The 3 patients received their last placebo dose 30 months from randomization. I thought that the next step was an End Of Treatment (EOT) Visit and that the crossover option was no longer offered at the end of the study. I put them in the non-crossover placebo group but that was wrong. They got the crossover option, IMO.
NYAS DATA = PFS KM curve. https://investorshub.advfn.com/uimage/uploads/2022/5/11/jjgyh5-10-22-Slide-11.png
13 placebo patients at risk at 24 month from randomization.
Zero placebo patients at risk at 36 months from randomization.
5 placebo patients with confirmed disease progression between 24 and 31 months from randomization.
8 placebo patients censored between 24 and 36 months from randomization.
A closer look at my “notes about censored placebo patients” also dampened my expectation.
I think only a few non-crossover placebo patients are alive 36 months from surgery, all with a poor prognosis.
All IMO.
Is MIA approval required before the MAA application can be filed ?
Nov.1, 2021
"You are correct that a facility manufacturing an ATMP must have a current GMP Certificate to manufacture either an IMP(material for clinical trials) or an MA product.
If the facility is in the UK or EU it must also hold either a Manufacture Import Authorisation MIA or a Manufacture Import Authorisation for Investigational Medicinal Products MIA(IMP) depending on what product is being manufactured. If in the UK the facility/company must apply to the MHRA for an MIA or MIA(IMP) and this process could take 90 days, during which time an inspection will also be carried out at the facility. Depending on the time taken to close out the inspection and issue the GMP certificate/s this may be longer than 90 days especially if there are any issues found at the inspection. This application can be made at the same time as the MA application so long as there is an intention to manufacture product at the manufacturing site. However, it should be noted that the processes are independent of one another and an MIA and or GMP Certificate must be in place for the manufacturing facility before the Marketing Authorisation can be granted."
Richard Parker
Senior GMDP Inspector
Inspection, Enforcement and Standards
MHRA, 10 South Colonnade, Canary Wharf, London E14 4PU
Gary,
Around 35 of the TOP 100 are placebo patients.
Thanks for sharing meirluc but i do not agree.
30 or 31 placebo patients are alive 32.9 months from randomization. (36 months from surgery)
13 DCVax-l patients died between 32.9 and 36 months from randomization.(See NYAS data)
I have no idea how many placebo patients died between 32.9 and 36 months from randomization but I don't believe that 33 placebo patients are still alive 36 months from randomization.
88 or 89 patients are at risk 36 months from surgery. (32.9 months from randomization)=
58 (13 + 45) DCVax-L patients at risk 36 months from surgery.
30 or 31 placebo patients at risk 36 months from surgery. (I guess 1/3 from the non cross-over group. Look at the number of placebo patients at risk 24 months from randomization on the PFS KM curve = 13 patients )
That’s definitely the EDEN system all right.
This only confirms that EDEN IS READY, and IS part of the commercial application at Sawston. That appears to be the prototype model of the EDEN system with all the commercial specifications that will be used for mass production by a contract manufacturer. And yes, it also confirms that there is one culture cartridge per unit.
May I ask how long ago you discovered this?
Happy Birthday Margaret!
Flaskworks EDEN device.
Recent Projects
Cellular Therapy
A funding-milestone prototype was developed for a cellular therapy device. The system produces immuno-therapeutics and dendritic cell-based vaccines. Project scope included mechanical engineering, system block diagram development and simplification, actuator selection and testing, CAD, prototype fabrication and assembly.
Quote:
• Upscaling other sites for regulatory compliance and commercial readiness
I wonder, then, if this could be referring to the new building on 6100 Global Drive?
XXXXX,
I drove by the 6100 Global site late last week. It appeared no construction had started. The parking lot had only one car. There were a few pallets of what could be construction material, but I’m unsure.
Looking through an open side door, that the place continues to be a cavernous like a warehouse.
I did receive a response to my questions yesterday from Charles River Laboratories. Their communications person checked with the Memphis site director, and told me that (1) no changes are planned to the original expansion plan that was awarded the public incentives (2) 4600 Shelby Drive is now undergoing expansion construction to double its size and that work should be completed by late 2022 and (3) the space at 6100 Global Drive will be used for additional capacity required for making personalized therapeutics.
I mean OS KM curves between 0 and 32,9 months from randomization. ( between 0 and 36 months from surgery)
I agree eagle8. Thanks.
The 2018 SNO presentation estimated that 36 months past surgery (33 months past randomization), 87 patients were still at risk. I am estimating that at least 80 such patients still existed 3 months later (at 36 months past randomization). The November 2018 SNO estimate was perhaps made a few months earlier than November but at that time probably all the trial's living patients were at least 30 months on trial and that estimate was therefore pretty accurate.
So of at least 80 post 36 months survivors, I have estimated a total of about 58 post 36 months survivors in the Treatment group. Therefore at least about 22 would be found in the group of 99 intend to cross over group.
Thank you Danish Dude.
https://mobile.twitter.com/FlemmingBruce/status/1552232963668156418/photo/1
Mike Scott .
President at Advent Bioservices
Thank you Fanny, yes we now have more than 50 staff. There is huge competition
for skilled people in this sector but Advent has really bucked the trend with some
impressive recruits. And we are looking for more! Hope all good in Leipzig.
Newly Diagnosed GBM: Significant Residual Disease Slide
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=168826841
1 out of 163 ECA patients (Newly Diagnosed GBM: Significant Residual Disease) alive 36 months from randomization.
14 out of 86 DCVax-L patients (Newly Diagnosed GBM: Significant Residual Disease) alive 36 months from randomization.
That's what counts Ex.
Ex,
Newly Diagnosed GBM: Significant Residual Disease Slide
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=168826841
86 dcvax-L patients and 163 ECA patients at risk. Do you believe there are patients with biopsies in that cohort of 163 ECA patients? (Newly Diagnosed GBM ECA : n=1366)
As far as the other RAs, all they have said is that the changed endpoint is safe and ethical. The acceptance of the IND protocol change in no way says they agree it is suitable for approval.
Dear XXXXX
Generally spoken your assumption should be right. For a definitive answer we would need the EudraCT numbers to be able to cross check.
Kind regards
H. Krafft
.....................................................
Dr. H. Krafft
Referatsleiter Klinische Prüfungen
Head, Section Clinical Trials
Paul-Ehrlich Institut
Paul-Ehrlich-Str. 51-59
D-63225 LANGEN
Dear H.Krafft,
Thank you for the reply. Much appreciated!
Here is the EudraCT number: 2011-001977-13 (European Union Clinical Trials Register).
https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001977-13/DE
Is my assumpion about the study above still correct?
Best,
XXXXX
Dear XXXXX
For the mentioned Clinical trial (2011-001977-13) recent changes of the protocol/IB were subjected to substantial amendment procedures including explicit approval and rejection parts.
Due to our national law in the assessment of substantial amendment, grounds for non-acceptance could not be raised in Germany. So any substantial amendment applicaction is decided either positive, negative or negative on single parts. The result of the assessment can be found and reflecting the changes/ adaptions in the EU register after the entering the sponsor information into EudraCT by the national Competent Authorities. Errors in this process are possible. If you have any issue with the endpoint of this clinical trial, we would ask you to contact primarily the sponsor of the clinical trial. In the meantime we are open for any constructive suggestions/ criticisms.
Kind regards
H. Krafft
THE SOCIETY OF UNIVERSITY NEUROSURGEONS
Prague, Czech Republic
2022 ANNUAL MEETING
June 29th-July 3rd, 2022
Linda Liau:
"In conclusion, the addition of DCVax-L to SOC resulted in a clinically meaningful and statistically significant extension in overall survival for both nGBM and rGBM".
https://static1.squarespace.com/static/55d34232e4b0a3f1fd2a226a/t/62c6e8fdc8ae1c1cb61ae488/1657202946459/Website+SUN+2022.pdf
Thanks pgsd and ATLnsider.
Linda Liau and her husband Marvin Bergsneider in Praque. (July 2022)
https://universityofmiamineurosurgery.smugmug.com/SUN/Prague-2022/i-2hLmG4V/A
https://universityofmiamineurosurgery.smugmug.com/SUN/Prague-2022/i-QpFdhPm/A
There could be DCVax-L approval before the commercial manufacturing certification.
Dear XXXXX
Thank you for your email.
You are correct that a facility manufacturing an ATMP must have a current GMP Certificate to manufacture either an IMP(material for clinical trials) or an MA product.
If the facility is in the UK or EU it must also hold either a Manufacture Import Authorisation MIA or a Manufacture Import Authorisation for Investigational Medicinal Products MIA(IMP) depending on what product is being manufactured. If in the UK the facility/company must apply to the MHRA for an MIA or MIA(IMP) and this process could take 90 days, during which time an inspection will also be carried out at the facility. Depending on the time taken to close out the inspection and issue the GMP certificate/s this may be longer than 90 days especially if there are any issues found at the inspection. This application can be made at the same time as the MA application so long as there is an intention to manufacture product at the manufacturing site. However, it should be noted that the processes are independent of one another and an MIA and or GMP Certificate must be in place for the manufacturing facility before the Marketing Authorisation can be granted.
If the facility performing the manufacture is outside of the UK but in the EU it is a the current time the responsibility of the competent authority in that country to carry out such an inspection and issue the manufacturing authorisations, which are recognised by the UK.
If the site is a third country then MHRA would carry out an inspection of that facility and issue a GMP Certificate only. The marketing authorisation applicant must highlight that this is the case so that an inspection can be arranged if required.
Further guidance and application forms can be found on our website:
https://www.gov.uk/guidance/apply-for-manufacturer-or-wholesaler-of-medicines-licences
I hope that this is of help to you.
Kind regards
Rick
Richard Parker
Senior GMDP Inspector
Inspection, Enforcement and Standards
MHRA, 10 South Colonnade, Canary Wharf, London E14 4PU
Funny...
June 23, 2022
Pietro Ivo D'Urso MD FRCS@pidurso
#BNOS2022 if anyone can, Ash…Kan! Fantastic presentation of Prof Ashkan: exciting results from the Phase 3 trial of #DCVax-L in Glioblastoma
@BNOSofficial@KingsNeuro
#BNOS2022 if anyone can, Ash…Kan! Fantastic presentation of Prof Ashkan: exciting results from the Phase 3 trial of #DCVax-L in Glioblastoma @BNOSofficial @KingsNeuro pic.twitter.com/xDpZBYnZa1
— Pietro Ivo D'Urso MD FRCS (@pidurso) June 23, 2022
BNOS@BNOSofficial
Congratulations Pietro - you have won our Twitter competition for the most Likes for this tweet! The prize is a ticket for the gala dinner at #BNOS2023 in Manchester. Please contact Liz@bnos.org.uk when registering next year. Well done!
Congratulations Pietro - you have won our Twitter competition for the most Likes for this tweet! The prize is a ticket for the gala dinner at #BNOS2023 in Manchester. Please contact Liz@bnos.org.uk when registering next year. Well done! 🏆
— BNOS (@BNOSofficial) June 27, 2022
It's possible Dr. Brem was asked this already. Perhaps his reply was to direct the search to this very article and presentation.
Could this be what Brem was referring to at the NYAS presentation with respect to each trial participant being "their own control"?
https://doi.org/10.1093/neuonc/noab276